Selective acylation of polysaccharides is desirable to tailor their structural and functional properties, hydrophobicity and hydrophilicity, interfacial properties, and biocompatibility. E.g., fatty acid esters of saccharides and polysaccharides may be useful as bioerodable drug delivery matrices, and biodegradable emulsifiers, compatibilizers, and detergents..sup.1 However, selective acylation of polysaccharides by chemical reactions are difficult due to the lack of specificity, solubility, and the multifunctionality of the polymer..sup.2 Enzymes have been used to acylate saccharides (up to 5 glucose moiety) regioselectively under mild conditions in organic solvents..sup.2-4 Similar reactions with polysaccharides would be desirable. However, the lack of solubility of these polymers and the enzymes in organic solvents implies significant problems in carrying out these conversions. Accordingly, alternative methods of achieving a functionally significant degree of acylation are required..sup.5-7
Enzymes are powerful catalysts in organic solvents where they catalyze a wide variety of reactions that are difficult to perform in aqueous solutions. This is particularly evident in transesterification reactions catalyzed by lipases and proteases wherein a variety of nucleophiles act as substrates for enzyme-catalyzed acyl transfer in nearly anhydrous organic solvents. Unfortunately, many polyhydroxylated compounds are either sparingly soluble in only the most polar organic solvents, or are completely insoluble in organic media. For these substrates, conventional non-aqueous enzymology is unable to support catalytic transformations. The development of a suitable technique for the selective modification of polysaccharides in organic solvents, therefore, would represent both an opportunity for the synthesis of novel materials as well as a means to overcome a technical hurdle in the broader uses of enzymes in non-aqueous media.
Accordingly, it is an object of this invention to overcome the above illustrated inadequacies and problems of insoluble polysaccharides by providing an improved method of their transesterification.
It is another object of this invention to provide a method of acylating polysaccharides wherein their selective modification results in structural and/or functional benefits.
Yet another object of the present invention is to provide a method of enabling the use of enzymes to catalyze reactions in non-aqueous media for the synthesis of bioerodable and biocompatible compounds.